Last reviewed: 20 Sep 2020
Last updated: 26 Aug 2020



History and exam

Key diagnostic factors

  • presence of risk factors
  • dermatitis
  • insomnia, depression, or memory loss
  • intermittent stupor
  • hallucinations or delirium
  • weakness
  • peripheral neuropathy
  • oppositional hypertonus or myoclonus
  • cogwheel rigidity
  • primitive reflexes
  • ataxia
  • nausea, vomiting, or diarrhoea
  • glossitis, cheilitis, or stomatitis

Other diagnostic factors

  • fatigue
  • anxiety or paranoia
  • anorexia, weight loss, or cachexia
  • headache
  • vertigo
  • incontinence
  • constipation
  • heartburn
  • angular palpebritis

Risk factors

  • malnutrition
  • chronic alcohol use disorder
  • vitamin B2 (riboflavin) deficiency
  • vitamin B6 (pyridoxine) deficiency
  • malabsorption
  • eating disorders
  • Hartnup's disease
  • carcinoid syndrome
  • antituberculous drugs
  • Crohn's disease
  • HIV infection
  • copper deficiency
  • certain drugs
  • pregnancy and lactation
  • age >65 years
  • Alzheimer's dementia
  • Parkinson's disease

Diagnostic investigations

1st investigations to order

  • serum tryptophan
  • urinary N-methylnicotinamide
  • urinary N-methyl-2-pyridone-5-carboxamide
  • urinary 2-pyridone/N-methylnicotinamide ratio
  • skin biopsy
  • photosensitivity testing
  • FBC
  • serum albumin
  • serum protein
  • LFTs
  • gamma-GT
More 1st investigations to order

Investigations to consider

  • serum total iron
  • iron-binding capacity
  • ferritin
  • transketolase activity
  • thiamine pyrophosphate (TPP)
  • riboflavin coefficient
  • serum pyridoxal-5-phosphate
  • serum cyanocobalamin
  • serum folic acid
  • red cell folic acid
  • stool examination
  • neutral aminoaciduria
  • serum serotonin
  • platelet serotonin
  • urinary 5-hydroxyindoleacetic acid
  • HIV antibodies
  • mental-state examination
  • ECG
More investigations to consider

Treatment algorithm


Senior Research Specialist

Centre for the Study of the Social and Environmental Determinants of Nutrition

Population Health, Health Systems and Innovation


Cape Town

South Africa


WP declares that she has no competing interests.


School of Public Health

University of the Western Cape

Cape Town

South Africa


ZJM declares that she has no competing interests.

Professor Emeritus

Stellenbosch University

Professor Extraordinaire

University of Limpopo

South Africa


DL declares that he has no competing interests.

Dr Whadi-ah Parker, Dr Zandile J Mchiza, and Dr Demetre Labadarios would like to gratefully acknowledge Dr Nelia Patricia Steyn, a previous contributor, as well as Miss Nophiwe Job, Ms Nwabisa Tshefu, and Mr Machoene Derrick Sekgala for their contributions to this topic. NPS, NJ, NT, and MDS declare that they have no competing interests.

Peer reviewersVIEW ALL

Emeritus Professor of Clinical Chemistry

University of Liverpool



AS declares that he has no competing interests.


Queens College

City University of New York



AM declares that he has no competing interests.

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